The Development of Prospective Primary School Science Teachers’ TPaCK Fostered by Innovative Science-Teacher Education

The EEdnaS study “Development and testing of digitally enriched science-related subject matter teaching in digital teaching-learning labs and university classrooms” aims to promote the professional competencies of prospective teachers that are needed for teaching science content in a world shaped by digitalization. To achieve this goal, university teaching units (seminars) that directly address cognitive components of a teacher’s professional competencies, which are important to teaching science content in primary school education, were developed. In addition, prospective teachers were asked to plan, implement, and evaluate primary school science education with a particular focus on digitization, as well as sharing the developed units as open-educational resources. This article reports on the impact of the first part of the seminar concept, in which the promotion of digitization-related, subject-specific teaching methodology, as well as content-related knowledge (TPaCK) was systematically promoted. In a standardized survey, it could be shown that the prospective teachers demonstrated positive developments, particularly in the components PCK, TCK, TPK, as well as TPaCK, regarding the self-efficacy in cognitive characteristics about one’s own ability within the reference frame of self. Furthermore, the development of knowledge, especially in the areas of TK, PCK, TCK, and TPK, could also be determined, but not in relation to TPaCK itself

PITX1 is a regulator of TERT expression in prostate cancer with prognostic power

Simple Summary Most prostate cancer is of an indolent form and is curable. However, some prostate cancer belongs to rather aggressive subtypes leading to metastasis and death, and immediate therapy is mandatory. However, for these, the therapeutic options are highly invasive, such as radical prostatectomy, radiation or brachytherapy. Hence, a precise diagnosis of these tumor subtypes is needed, and the thus far applied diagnostic means are insufficient for this. Besides this, for their endless cell divisions, prostate cancer cells need the enzyme telomerase to elongate their telomeres (chromatin endings). In this study, we developed a gene regulatory model based on large data from transcription profiles from prostate cancer and chromatin-immuno-precipitation studies. We identified the developmental regulator PITX1 regulating telomerase. Besides observing experimental evidence of PITX1′s functional role in telomerase regulation, we also found PITX1 serving as a prognostic marker, as concluded from an analysis of more than 15,000 prostate cancer samples. Abstract The current risk stratification in prostate cancer (PCa) is frequently insufficient to adequately predict disease development and outcome. One hallmark of cancer is telomere maintenance. For telomere maintenance, PCa cells exclusively employ telomerase, making it essential for this cancer entity. However, TERT, the catalytic protein component of the reverse transcriptase telomerase, itself does not suit as a prognostic marker for prostate cancer as it is rather low expressed. We investigated if, instead of TERT , transcription factors regulating TERT may suit as prognostic markers. To identify transcription factors regulating TERT , we developed and applied a new gene regulatory modeling strategy to a comprehensive transcriptome dataset of 445 primary PCa. Six transcription factors were predicted as TERT regulators, and most prominently, the developmental morphogenic factor PITX1. PITX1 expression positively correlated with telomere staining intensity in PCa tumor samples. Functional assays and chromatin immune-precipitation showed that PITX1 activates TERT expression in PCa cells. Clinically, we observed that PITX1 is an excellent prognostic marker, as concluded from an analysis of more than 15,000 PCa samples. PITX1 expression in tumor samples associated with (i) increased Ki67 expression indicating increased tumor growth, (ii) a worse prognosis, and (iii) correlated with telomere length

The Ternary Rab27a–Myrip–Myosin VIIa Complex Regulates Melanosome Motility in the Retinal Pigment Epithelium

The retinal pigment epithelium (RPE) contains melanosomes similar to those found in the skin melanocytes, which undergo dramatic light-dependent movements in fish and amphibians. In mammals, those movements are more subtle and appear to be regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and MyoVIIa-interacting protein, Myrip, promotes the formation of a functional tripartite complex. In heterologous cultured cells, all three proteins co-immunoprecipitated following overexpression. Rab27a and Myrip localize to the peripheral membrane of RPE melanosomes as observed by immunofluorescence and immunoelectron microscopy. Melanosome dynamics were studied using live-cell imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either stationary or slow movement interrupted by bursts of fast movement, with a peripheral directionality trend. Nocodazole treatment led to melanosome paralysis, suggesting that movement requires microtubule motors. Significant and similar alterations in melanosome dynamics were observed when any one of the three components of the complex was missing, as studied in ashen- (Rab27a defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE cells transduced with adenovirus carrying specific sequences to knockdown Myrip expression. We observed a significant increase in the number of motile melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and inversion of directionality. Similar alterations were observed upon cytochalasin D treatment, suggesting that the Rab27a–Myrip–MyoVIIa complex regulates tethering of melanosomes onto actin filaments, a process that ensures melanosome movement towards the cell periphery

Predicting breast tumor proliferation from whole-slide images : the TUPAC16 challenge

Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is a highly subjective and labor-intensive task. Previous efforts to automate tumor proliferation assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohen's kappa score of κ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearman's correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first comparison study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labeled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task

The Development of Prospective Primary School Science Teachers’ TPaCK Fostered by Innovative Science-Teacher Education

The EEdnaS study “Development and testing of digitally enriched science-related subject matter teaching in digital teaching-learning labs and university classrooms” aims to promote the professional competencies of prospective teachers that are needed for teaching science content in a world shaped by digitalization. To achieve this goal, university teaching units (seminars) that directly address cognitive components of a teacher’s professional competencies, which are important to teaching science content in primary school education, were developed. In addition, prospective teachers were asked to plan, implement, and evaluate primary school science education with a particular focus on digitization, as well as sharing the developed units as open-educational resources. This article reports on the impact of the first part of the seminar concept, in which the promotion of digitization-related, subject-specific teaching methodology, as well as content-related knowledge (TPaCK) was systematically promoted. In a standardized survey, it could be shown that the prospective teachers demonstrated positive developments, particularly in the components PCK, TCK, TPK, as well as TPaCK, regarding the self-efficacy in cognitive characteristics about one’s own ability within the reference frame of self. Furthermore, the development of knowledge, especially in the areas of TK, PCK, TCK, and TPK, could also be determined, but not in relation to TPaCK itself

Fachliche Perspektiven auf digitalisierungsbezogene Lernangebote in der Ausbildung von Grundschullehrer*innen

Unter einem gemeinsamen Dach verstehen sich die Leipziger Hochschullernwerkstätten als Orte experimentellen, entdeckenden und forschenden Lernens für Studierende und Lehrende. Der folgende Beitrag stellt das räumlich und konzeptionell strukturierte Leipziger Modell verbundener Hochschullernwerkstätten vor und fokussiert die Implementierung digitalisierungsbezogener Lernangebote. Am Beispiel ausgewählter Inhalte der Fachbereiche Deutsch, Mathematik und Sachunterricht werden die zugrunde liegenden Prinzipien der Lernwerkstattarbeit in ihrer Verknüpfung mit innovativen Praktiken fachlichen Lernens vorgestellt und kritisch diskutiert: In Seminarprojekten planen, erproben und evaluieren Studierende des Sachunterrichts digitalisierungsbezogene Lernaufgaben für und mit Schüler*innen. Als „geschützter Raum“ spielen die räumlichen und inhaltlichen Ressourcen der Hochschullernwerkstatt Lehrsammlung Sachunterricht hierbei eine besondere Rolle, bevor anschließend eine Erprobung und Evaluation in Grundschulen erfolgt. Vor dem Hintergrund aktueller bildungspolitischer Debatten setzen sich Studierende des Fachbereichs Mathematik kritisch mit den häufig gegensätzlich gebrauchten Begriffen „analog“ – „digital“ auseinander und erkunden, auch in Verbindung mit Schulklassen, anhand von Apps und digitalen Tafeln mögliche Ergänzungen analoger Anschauungsmaterialien im Fach Mathematik. Im LiteracyLab lernen Studierende des Faches Deutsch die spezifischen Rezeptions- und Partizipationsmöglichkeiten von Kinderliteratur im Medienverbund kennen und vertiefen ihre didaktischen Kompetenzen gezielt im Hinblick auf die adaptive Gestaltung von Formen der Literaturvermittlung im Zeitalter der Digitalität. Die exemplarische Darstellung zeigt, wie digitalisierungsbezogene Lernangebote den Studierenden wichtige Erprobungs- und Reflexionsräume bieten und wie Erkundung und Reflexion neuer didaktischer Modellierungen zum Professionalisierungsprozess in der Lehramtsausbildung beitragen können. (DIPF/Orig.

Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1

Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex